Ventilation assist devices may be required for patients suffering from Spinal Cord Injuries (SCI) and brain injuries. In particular as a result of trauma or disease, SCI account for 40 cases per million in the United States, according to the National Spinal Cord Injury Statistical Center (NSCISC, 2014). Approximately 276,000 Americans (0.1% of the US population) are SCI survivors, with 12,500 new injuries in the US being reported each year. Signs and symptoms experienced by a patient will vary depending on where the spinal cord is injured and the extent of the injury. It will also depend upon which part of the body that the injured area of the spinal cord innervates. In particular, injury to the spinal cord can cause problems with voluntary motor control of a myotome (a group of muscles innervated through a specific part of the spinal cord). The muscles may contract uncontrollably, become weak, or be completely paralyzed. The loss of muscle function can have additional effects when the muscle is not used, including disuse atrophy of the muscle and bone degeneration. Fortunately, many cases of disuse atrophy can be reversed with exercise.
The most common site of injury occurs in the cervical cord (representing 54% of all cases), which may lead to partial or complete tetraplegia, also known as quadriplegia. Damage to the cervical spinal cord may also lead to depreciated functioning of the primary muscle for breathing—the diaphragm (a thin sheet of muscle supporting the lungs and separating the thoracic cavity containing the heart and lungs, from the abdominal cavity). This depreciated functioning of the diaphragm is due to the impact of the injury upon the nerves supplied to the diaphragm from the phrenic motor neurons in the damaged cervical spinal cord. In particular, the phrenic nerve stems from cervical spinal nerve roots C3, C4, and C5, which innervate the diaphragm, and thereby, enable breathing. Under normal functioning, as the diaphragm contracts, the volume of the thoracic cavity increases and air is drawn into the lungs. If the spinal cord is contused above cervical spinal nerve root C3, then spontaneous breathing may be not possible. Accordingly, people with high-level cervical SCI may also have partial or complete loss of ventilatory control because of diaphragmatic paralysis.
Ventilation may also be further impaired due to paralysis of the external intercostal muscles, which help to expand and stabilize the rib cage during breathing. Additionally, the paralysis of the abdominal muscles, which sometimes are engaged for active expiration, or internal intercostal muscles used for forceful exhalation such as coughing or under exercise may also impair ventilation. Both sets of these muscles are innervated by motor neurons that are distributed across the thoracic (chest) region of the spinal cord (levels T1 to T11). To further complicate the consequences of SCI, diseases of the respiratory system are the leading cause of death after a SCI according to the NSCISC, where, 66.9% of these reported deaths resulted from pneumonia.
Most people with paralysis of the respiratory muscles require ventilation management and are initially supported using positive pressure-mechanical ventilation, where air (or another gas mix) is pumped through a tube inserted into the mouth and down into the trachea. However, this form of assisted mechanical ventilation is associated with significant discomfort, diaphragm atrophy, atelectasis, and barotrauma. In particular, the use of a mechanical ventilator may sometimes cause the muscles of the diaphragm to atrophy, which can occur after as little as 18 to 69 hours of complete diaphragmatic inactivity. Further, as a result of diaphragm atrophy, autonomous respiratory recovery is delayed. Moreover, the patient may become dependent upon the use of a mechanical ventilator, causing the muscles of the diaphragm to fatigue quickly without ventilation assistance, thereby making it difficult for the patient to breathe on their own for an extended period of time.
Fortunately, diaphragmatic pacing through electrical stimulation of the diaphragm may eliminate muscle atrophy, where laparoscopic implantation of intramuscular electrodes is used to stimulate the diaphragm. Particularly, diaphragmatic pacing in both adults and children can help wean patients off the mechanical ventilator, since diaphragmatic pacing has been proven to strengthen the diaphragm. Diaphragmatic pacing may also be beneficial for patients with central alveolar ventilation (sleep apnea) and Chronic Obstructive Pulmonary Disease (COPD). However, electrical stimulation of the diaphragm causes the diaphragm muscles to fatigue quickly. As such, diaphragmatic pacing through electrical stimulation not only limits the time off of the mechanical ventilator, but also does not allow enough time for therapeutic strengthening of the muscles of the diaphragm. In the alternative, electrical stimulation of the phrenic nerve for diaphragm pacing has been clinically accepted as an alternative for ventilator-dependent people with tetraplegia. Yet, for patients without intact phrenic nerves or unilateral phrenic function, clinicians must resort to laparoscopic implantation of intramuscular electrodes to stimulate the diaphragm.
Commercially available diaphragmatic pacing systems developed to-date employ an open-loop ventilatory control system to deliver electrical impulses through the implanted electrodes. Despite being widely used, however, open-loop control systems possess time consuming iterative manual tuning of stimulation parameters, which does not compensate for reduced diaphragmatic contraction due to muscle fatigue. Further, the current diaphragmatic pacing systems cannot respond to unanticipated changes or episodes of high metabolic demand, where metabolic demand represents the amount of oxygen necessary for the heart to convert chemical energy into mechanical work.